Nanostructured Lipid Carriers Gel Research Articles

Betulin-NLC-hydrogel for the Treatment of Psoriasis-like Skin Inflammation: Optimization, Characterisation, and In vitro and In vivo Evaluation.

Psoriasis is a chronic inflammatory skin disorder that poses significant challenges regarding effective and targeted drug delivery. Bioactive substances like betulin have shown tremendous utility in treating these conditions; however, they pose limited utility owing to their physicochemical characteristics. Here, we aimed to develop a novel topical dosage form for treating psoriasis, utilising betulin-loaded solid lipid nanoparticles (NLCs) incorporated into a hydrogel matrix. The optimization of the formulation was meticulously conducted using a design of experiments methodology, and its diverse physicochemical attributes were thoroughly examined. Evaluating betulin's in vitro release pattern from the NLC-hydrogel demonstrated consistent and regulated drug release properties. Additionally, the formulation demonstrated improved skin penetration abilities as determined by in vitro skin permeation experiments employing Franz diffusion cells- furthermore, the therapeutic effectiveness of the betulin-NLC-hydrogel was assessed by an in vivo experiment carried out using an imiquimod-induced psoriasis-like skin inflammation model in BALB/c female mice. The NLCs exhibited a pH of 5.67±0.86, particle size of 148.16±12.66 nm, and zeta potential of -22.84±2.37 mV, ensuring stability and suitability for topical use. The gel, with a pH of 6.05±0.43 and viscosity of 17550±120 cPs, showed enhanced skin hydration and lipid restoration. Drug release studies indicated a slower release from NLCs and gel, improving skin retention. Stability tests revealed that the formulations were stable at room temperature but not at elevated temperatures. The in vitro safety profile of the formulation revealed no significant adverse effects on HaCaT cell lines. The NLC gel demonstrated significant anti-psoriatic activity, reducing inflammation and cytokine levels. The betulin-NLC-hydrogel formulation exhibited promising characteristics for the topical treatment of psoriasis, showcasing optimised drug delivery, sustained release, and notable therapeutic efficacy. The findings from this study provide a foundation for the potential clinical translation of this innovative topical dosage form for improved psoriasis management.

Preparation and Evaluation of Itraconazole Nanoparticle Lipid Carrier Gel for Dermatophytosis

Fungal infection is one of the common dermatological diseases. Drug delivery systems for topical use have shown significant advantages in targeting the drug to the action site in the body and also reduces the systemic side effects. Itraconazole was chosen as a model drug with low aqueous solubility. In the present study an attempt was made to prepare itraconazole loaded nanostructured lipid carrier (NLC). Different formulations were prepared by hot homogenization technique using solid lipid and liquid lipid (Compritol 888 & Caprol PGE 860) and surfactants (Poloxamer 188, tween 80). All the Formulations were characterized for drug content, entrapment efficiency, particle size, poly dispersity index, zeta potential &in vitro drug release and FTIR was done to study any interaction between excipients. The best formulation shows better drug release and entrapment efficiency 83.2%. the best formulation F3 showed better in-vitro drug release 55.46% at the end of 8th hour. The F3 was made into gel using Carbopol as a gelling agent. SEM study revealed that the NLC gel shows the particle size was found to be 500 nm in size smooth surfaces. NLC gel shows Drug release of NLC gel followed non- Fickian diffusion. NLC gel were stable at 40 ± 2ֹ°C and 75 ± 5% RH. Thus, the prepared NLC gel proved to be a potential candidate as a topical nanoparticulate sustained drug delivery system for itraconazole (BCS class II drug). keywords: Itraconazole, Nanoparticle Lipid Carrier, Lipids.

Preparation and characterisation of esculetin-loaded nanostructured lipid carriers gels for topical treatment of UV-induced psoriasis

Significance As an inflammatory and autoimmune skin condition, psoriasis affects 2–3% of people worldwide. Psoriasis requires prolonged treatments with immunosuppressive medications which have severe adverse effects. Esculetin (Esc) is a natural medication that has been utilised to treat psoriasis. Objective The goal of this work is to improve Esc’s solubility by developing novel Esc nanostructured lipid carriers (NLCs) for treating psoriasis and increasing the residence time on the skin which infers better skin absorption Methods The particle size, zeta potential and entrapment efficiency (EE) of Esc NLCs were assessed. Incorporating NLCs into gum Arabic gel preparation enhances their industrial applicability, absorption and residence time on the skin. Esc NLC gels were evaluated by in vitro release and in vivo effectiveness on a rat model of UV-induced psoriasis. Results Esc NLCs showed high EE reaching more than 95% and reasonable particle size ranging between (53.86 ± 0.38 to 236.3 ± 0.11 nm) and were spherical. The release study of Esc NLCs gel demonstrated a fast release of Esc denoting enhanced bioavailability. Compared to free Esc, Esc NLCs gel (F2) could considerably lower the level of CD34 and TNF-α in the skin. The results were validated through histopathological analysis. Conclusion As Esc NLCs gel (F2) has strong anti-inflammatory properties, our results showed that it presented a significant potential for healing psoriasis.

Antipsoriatic Effect of Silymarin NLCs Based Gel: In Vitro and In Vivo Activity.

Psoriasis is a chronic inflammatory disorder affecting over 100 million people, requires long-term therapy. Current treatments offer only symptomatic relief. However, phytoconstituents-based therapies like Silymarin (SLM) have shown promising effects. The study aims to develop, optimize, and evaluate a novel stable SLM NLC gel to improve anti-psoriatic activity by enhancing its permeability and retention into the dermal layer. SLM NLC formulation was prepared and optimized using 32 full factorial designs. The formulation was evaluated for the particle size, PDI, zeta potential, and % entrapment efficiency, evaluated by Transmission electron microscopy and thermal analysis. The freeze dried and prepared NLC-loaded gel was evaluated for physicochemical parameters, ex-vivo, and in-vivo studies. SLM-loaded NLC shows 624nm particle size, 0.41 PDI, 92.95% entrapment efficiency, and -31.6mV zeta potential. The sphere form of NLCs was confirmed using TEM. Controlled drug release was observed in ex vivo studies, low PASI score compared to disease control. Further, the levels of IL-6, TNF-α, and NF-κB were also reduced. The results are supported by histopathology showing minimal parakeratosis indicated in the SLM NLC-treated group. Prepared NLC-based shows enhance topical penetration and decrease the thickness of psoriatic plaques in the in vivo study.

FORMULATION OF NANOSTRUCTURED LIPID CARRIER GEL FROM CALLUS EXTRACT OF MULBERRY LEAF (MORUS ALBA L.) WITH 2, 4-DICHLORO PHENOXY ACETIC ACID AND BENZYL AMINO PURINE AS CALLUS GROWTH FACTOR

Objective: This research aimed to formulate the callus extract of mulberry leaf in the form of a Nanostructured lipid Carrier (NLC) gel. Methods: Dichlorophenoxyacetic acid (2,4–D) and Benzyl Amino Purine (BAP) was used as a callus growth factor. Callus leaf extracted with ethanol 96% by maceration-sonication method. An amount of 0.5% callus leaf extract was formulated into NLC. The NLC is then evaluated for its particle size and polydispersity index. The NLC gel is evaluated for its organoleptic, homogeneity, viscosity, flow ability, and pH. The callus extract and the NLC gel were also evaluated for their tyrosinase inhibitor activity. Results: The best formulation of NLC showed a particle size of 189.8 nm and a polydispersity index of 0.578. The NLC is a semi-solid, yellowish, odorless, homogeneous gel, with viscosity of 26,666.67 cPs, plastic-thixotropic type, pH of 5.26. The evaluation of tyrosinase inhibitory activity of the callus extract and the NLC gel showed IC50 value of 217.64 and 248.12 ug/ml. Conclusion: It can be concluded that leaf callus extract of mulberry can be formulated into an NLC gel that is physically and chemically stable and has good skin-lightening activity.

Improvement of lidocaine skin permeation by using passive and active enhancer methods

Lidocaine is generally recognized and preferred for local anaesthesia, but in addition, studies have described additional benefits of lidocaine in cancer therapy, inflammation reduction, and wound healing. These properties contribute to its increasing importance in dermatological applications, and not only in pain relief but also in other potential therapeutic outcomes. Therefore, the purpose of our study was to enhance lidocaine delivery through the skin. A stable nanostructured lipid carrier (NLC), as a passive permeation enhancer, was developed using a 23 full factorial design. The nanosystems were characterized by crystallinity behaviour, particle size, zeta potential, encapsulation efficiency measurements, and one of them was selected for further investigation. Then, NLC gel was formulated for dermal application and compared to a traditional dermal ointment in terms of physicochemical (rheological behaviour) and biopharmaceutical (qualitative Franz diffusion and quantitative Raman investigations) properties. The study also examined the use of 3D printed solid microneedles as active permeation enhancers for these systems, offering a minimally invasive approach to enhance transdermal drug delivery. By actively facilitating drug permeation through the skin, microneedles can complement the passive transport achieved by NLCs, thereby providing an innovative and synergistic approach to improving lidocaine delivery.

Development of Nanostructured Lipid Carrier-Loaded Flavonoid-Enriched Zingiber officinale.

Flavonoids, which are bioactive molecules found in Zingiber officinale, have been widely used as antioxidant and anti-inflammatory drugs. The presence of nanostructured lipid carriers (NLCs) as sophisticated delivery systems for bioactive compounds, such as flavonoids, can increase their bioavailability and stability, thus potentially producing better therapeutic effects. This study aimed to develop an anti-inflammatory topical gel using NLC-containing flavonoids derived from Zingiber officinale. The NLC formulation was prepared using stearic acid, a mixture of medium-chain triglycerides and isopropyl myristate, Tween 20, and Span 20 by using a hot homogenization method. The total flavonoid content obtained through sequential maceration stages was 4.04 mg of QUE/g of dry extract. The highest encapsulation efficiency of flavonoid-loaded NLC was observed at a flavonoid, Zingiber officinale extract (ZOE) concentration of 2%. It was found that a ZOE concentration of 0.4% provided excellent stability with a particle size of 302-344 nm and a polydispersity index of 0.14-0.23 after 28 days of observation. Morphological analysis of the ZOE-loaded NLC revealed a stable and well-developed formulation with a fairly uniform distribution. The presence of distinctive and uniformly distributed single particles suggests a promising alternative drug delivery system for conventional topical preparations. ZOE-loaded NLC gel showed solid-like properties and higher quality stability than the gel.

Topical delivery of Mannose Conjugated-Doxorubicin-Berberine nanostructured lipid carrier gel for skin cancer amelioration: Formulation optimization, in-silico, in-vitro, ex-vivo assessment, and dermatokinetic analysis

Mannose-conjugated doxorubicin (DOX) and berberine (BBR) loaded nanostructured lipid carriers (Ma-DB-NLC) topical gel was formulated for skin cancer treatment. DOX is a potent anticancer drug that was combined with BBR to synergize the clinical efficacy of the formulation in skin cancer treatment. The findings of the in-silico study indicated that DOX & BBR were the promising ligands of DNA-Topoisomerase-Ⅱ & p13k, with excellent docking scores. The central composite rotatable design (CCRD) was used to optimize the NLC formulation. The size, PDI, and Zeta Potential (ZP) of Ma-DB-NLC were 202.666 ± 0.907 nm, 0.364 ± 0.002 and −23.666 ± 1.048 mV respectively. The % entrapment efficiency (EE) of prepared formulation was found to be 89.491 ± 1.310 (DOX) and 88.480 ± 1.160 (BBR). Based on the results of permeation studies, Ma-DB-NLC gel has shown better permeation than conventional gel through the mice's skin and Strat-M™ membrane. Moreover, the dermatokinetic study revealed that Ma-DB-NLC gel was found with a better deposition profile. Furthermore, CLSM findings supported the permeation and dermatokinetic results which indicated greater deposition and retention of DOX and BBR into the deeper layer of skin than conventional gel. The prepared Ma-DB-NLC gel was found with better size, ZP, % EE, skin permeation, and deposition than conventional gel for skin cancer amelioration.

Optimized albendazole-loaded nanostructured lipid carrier gel: a redefined approach for localized skin cancer treatment

Fabrication and characterization of nanostructured lipid carrier (NLC)-based gel for localized delivery of albendazole (ABZ) against skin cancer.

Targeting Potential of Zinc Oxide Nanoparticles and Finasteride-loaded Nano Lipidic Carriers-infused Topical Gel - In vitro and In vivo Skin Permeation Studies

Background: There is an unmet clinical need to develop topical carriers for finasteride to reduce its systemic side effects in the treatment of androgenic alopecia (AGA). Zinc oxide (ZnO) nanoparticles have also emerged as an influential agent in hair biology. Aim: The main focus of the work was to develop a novel formulation to explore the potential of ZnO nanoparticles in combination with NLCs of finasteride (FIN) for topical delivery. Method: ZnO nanoparticles were synthesized by precipitation method and were subsequently incorporated within the Carbopol gel. The ZnO nanoparticles and the gel were evaluated for their physicochemical characteristics. In vitro release study was performed for the determination of release of the drugs from the gel and ex vivo study was conducted for the determination of penetration of the NLCs and ZnO nanoparticles into the skin. Result: The particle size of the nanoparticles was found to be 200 nm. The pH, viscosity and spreadability of the gel was observed to be 6.13±2.11, 35,845.3±6.97 cps at 5 rpm and 17.14±2.32 respectively. Ex vivo drug permeation and skin distribution studies of the NLC gel formulations carried on rat dorsal skin indicated 25.763±0.2 μg/cm² and 19.375±1.2 μg/cm² of FIN and ZnO in 12 hr respectively. Conclusion: The results indicated the potential of developed systems for topical drug delivery for treatment of androgenic alopecia.

Formulation of Nanostructured Lipid Carrier Gel From Mulberry Root Extract (Morus alba L.) as Whitening Agent using Zebrafish Modelling

Mulberry is a plant that has been shown to be effective as a whitening agent. The objective of this research was to evaluate the efficacy of mulberry root extract (MRE) and its nanostructured lipid carrier (NLC) extracts in terms of their ability to lighten skin tone by using zebrafish as a model. NLC were formulated into gel preparations. The whitening effect of MRE and NLC was evaluated, and the melanin content of the extracts was found to be the result of the evaluation. Based on the results of morphological observations, a decrease in melanin levels was seen in the eye. In the mulberry root extract, the melanin level decreased with an increase in the concentration of the mulberry root extract. In the NLC of mulberry root extract, a decrease in melanin levels was obtained at an increased NLC concentration of mulberry root extract. It can be concluded that mulberry root NLC has the ability to act as a whitening agent, which is distinguished by the reduction of melanin content.

Nanostructured Lipid Carriers to Enhance the Bioavailability and Solubility of Ranolazine: Statistical Optimization and Pharmacological Evaluations.

Chronic stable angina pectoris is the primary indication for ranolazine (RZ), an anti-anginal drug. The drug has an anti-ischemic action that is unaffected by either blood pressure or heart rate. Due to the first-pass effect, the drug has a reduced bioavailability of 35 to 50%. The study emphasized developing a novel transdermal drug delivery system of nanostructured lipid carriers (NLCs) for delivering RZ. Many pharmaceutical companies employ lipid nanoparticles as biocompatible carriers for medicinal, cosmetic, and biochemical uses. These carriers are appropriate for many applications, such as topical, transdermal, parenteral, pulmonary, and oral administration, because of the large variety of lipids and surfactants that are readily available for manufacturing. RZ NLCs were made using high-pressure homogenization. Statistical analysis was utilized to find the best formula by varying the concentrations of Precirol ATO 5 (X1), oleic acid (X2), and Tween 80 (X3). Variables such as entrapment effectiveness (EE) (Y1), particle size (Y2), polydispersity index (PDI) (Y3), and zeta potential (Y4) were tested. A variety of tests were performed on the new formulation to ascertain how well it would be absorbed in the body. These tests included in vivo absorption studies, skin permeability assessments, in vitro drug release assessments, and physicochemical analyses. The particle size of RZ-NLCs was shown to be very small (118.4 ± 5.94 nm), with improved EE (88.39 ± 3.1%) and low ZP and PDI (-41.91 ± 0.38 and 0.118 ± 0.028). SEM and TEM analysis confirmed the structure of the NLCs and showed a smooth, spherical surface. Improved RZ-NLCs were used to create NLC gel, which was then tested for elasticity both physically and rheologically. The formulation's elasticity was investigated. Optimized RZ-NLCs and NLCG were found to have transdermal fluxes of 48.369 g/cm2/h and 38.383 g/cm2/h, respectively. These results showed that the transdermal delivery of RZ distribution through NLC's transdermal gel had more significant potential. According to in vivo experiments, the drug's bioavailability in Wistar rats increased when it was delivered through NLCs. The findings demonstrated that NLCs loaded with RZ successfully transported the RZ to the designated site with no interruptions and that a quadratic connection existed between the independent and dependent variables.

Statistically Optimized Tacrolimus and Thymoquinone Co-Loaded Nanostructured Lipid Carriers Gel for Improved Topical Treatment of Psoriasis.

The aim of this investigation was to develop and analyze a tacrolimus and thymoquinone co-loaded nanostructured lipid carriers (TAC-THQ-NLCs)-based nanogel as a new combinatorial approach for the treatment of psoriasis. The NLCs were formulated by an emulsification-solvent-evaporation technique using glyceryl monostearate, Capryol 90 (oil), and a mixture of Tween 80 and Span 20 as a solid lipid, liquid lipid, and surfactant, respectively. Their combination was optimized using a three-factor and three-level Box-Behnken design (33-BBD). The optimized TAC-THQ-NLCs were observed to be smooth and spherical with a particle size of 144.95 ± 2.80 nm, a polydispersity index of 0.160 ± 0.021, a zeta potential of -29.47 ± 1.9 mV, and an entrapment efficiency of >70% for both drugs. DSC and PXRD studies demonstrated the amorphous state of TAC and THQ in the lipid matrix of the NLCs. An FTIR analysis demonstrated the excellent compatibility of the drugs with the excipients without interactions. The TAC-THQ-NLC-based nanogel (abbreviated as TAC-THQ-NG) exhibited a good texture profile and good spreadability. The in vitro release study demonstrated a sustained drug release for 24 h from the TAC-THQ-NG that followed the Korsmeyer-Peppas kinetic model with a Fickian diffusion mechanism. Moreover, the TAC-THQ-NG revealed significantly higher dose-dependent toxicity against an HaCaT cell line compared to a TAC-THQ suspension gel (abbreviated as TAC-THQ-SG). Furthermore, the developed formulations demonstrated antioxidant activity comparable to free THQ. Confocal microscopy revealed improved permeation depth of the dye-loaded nanogel in the skin compared to the suspension gel. Based on these findings, it was concluded that TAC-THQ-NG is a promising combinatorial treatment approach for psoriasis.

Nanostructured Etodolac Carriers in Transdermal Gel: Optimization and Characterization.

To optimize, formulate, and evaluate a Nanostructured Lipid Carrier (NLC) based transdermal gel of Etodolac (ETD). To avoid issues of conventional route ETD administration like first pass metabolism, gastric ulceration, hemorrhage, and being a class-II drug with less solubility. A transdermal gel of nanostructured lipid carrier for ETD has been developed. Formulation will execute faster onset of action, increased penetration, permeation with extended release of the drug for a longer duration. A central composite 32 factorial design is used to plan experiments. NLCs are prepared by the method of melt emulsification and ultrasonication. Compritol 888ATO and Miglyol are used as solid and liquid lipid phases. Surfactant Pluronic F68 showed a significant effect on particle size, entrapment efficiency, and drug release. Particle size characterized using photon correlation spectroscopy and scanning electron microscopy. Cumulative drug release studied using an artificial diffusion cell and a dialysis membrane. A skin permeation study was performed using goat skin at 32°C ± 0.5°C. The efficacy of the NLC gel was verified using a pharmacodynamic study followed by stability study for 3 and 6 months. The optimized batch of ETD NLC found spherical with a 241.3 nm particle size with 0.392 PDI,-29 mV zeta potential. Entrapment efficiency and cumulative drug release were found to be 64.21 ± 1.23% and 70.12 ± 2.10% (after 12 hours), respectively. All batches followed zeroorder drug release kinetics and non-Fickian (Super Case II transport) with 0.1619 mg/cm2/hr transdermal flux. The NLC gel of ETD showed a quick onset and lengthened therapeutic activity until 24 hours compared to the micellar ETD gel. Etodolac NLC batch successfully optimized using central composite design. The relationships between the components of the NLC-total lipid:drug and surfactant-and the outcomes- particle size,%entrapment and% drug release-were better understood by examining several contour plots. The results of the experimental and predicted formulations were found to be in good agreement with slight bias, demonstrating the reliability of the optimization process.

Simvastatin-Loaded Nanostructured Lipid Carriers as Topical Drug Delivery System for Wound Healing Purposes: Preparation, Characterization, and In Vivo Histopathological Studies.

Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, is a commonly used drug to reduce total cholesterol and low-density lipoprotein (LDL) levels. Furthermore, several mechanisms showed the wound-healing potential of statins, especially simvastatin. Simvastatin is a lipophilic drug, therefore, it has low water solubility with limited skin permeability potential. In this regard, nanostructured lipid carriers (NLCs) were recruited as novel topical drug delivery systems to enhance skin adhesion and film formation, maintain skin integrity, sustain the release of simvastatin, and prolong simvastatin skin deposition to help pressure ulcers healing and regeneration. NLCs were fabricated using the solvent diffusion evaporation technique. Drug loading, in vitro drug release, and morphological assessment on the optimized formulation were considered. Furthermore, in vivo effect of simvastatin-loaded NLCs gel on pressure ulcer healing was assessed using a rat skin model. Histopathological assessments were compared with conventional simvastatin gel and drug-free NLCs gel. Simvastatin-loaded NLC with an average diameter of 100 nm was considered as the optimum formulation. According to the results entrapment efficiency of simvastatin within the NLCs was about 99.4%. Drug release studies revealed sustained drug release from NLCs in which about 87% of the drug was slowly released during 48 hours. Animal study results confirmed that simvastatin-loaded NLCs gel has better efficacy on pressure ulcers and could significantly reduce inflammation, and promote skin regeneration compared to both drug-free NLCs and conventional simvastatin gels. Simvastatin-loaded NLCs with an average particle size of 100 nm would be a promising novel topical drug delivery system with sustained drug release potential for pressure ulcer treatment.

Designing and evaluation of dermal targeted combinatorial nanostructured lipid carrier gel loaded with curcumin and resveratrol for accelerating cutaneous wound healing

A nanostructured lipid carrier containing combined curcumin (CUR) and resveratrol (RSV) was prepared and tested for its potential to accelerate wound healing through topical administration. Prepared nano lipid carrier (NLC) formulation had a particle size of 132.3 ± 4.54 nm, polydispersity index (PDI) of 0.478, and zeta potential of −16.6 mV. Entrapment efficiency (EE) for CUR and RSV was found to be 94.21 ± 0.28% and 84.61 ± 0.15%, respectively. Drug loading was found to be 8.560 ± 0.948% (for CUR) and 7.602 ± 0.452% (for RSV). NLC formulation was converted to NLC gel by incorporation of Carbopol 934 for enhancing its dermal applicability. Flux and permeability coefficient for CUR and RSV in NLC gel was found to be 22.087 µg/cm2/h, 11.299 µg/cm2/h, and 0.2208, 0.1129, respectively, through goat ear skin and 19.213 µg/cm2/h, 22.66 µg/cm2/h and 0.1921, 0.2266, respectively, through Strat-MTM membrane. Dermatokinetic study revealed significant enhancement in Cskin max and AUC0–12h in skin sample treated with NLC gel in comparison with plain gel. Also, NLC gel showed longer retention time which indicates prolonged drug action at targeted site thus, NLC gel may show better therapeutic efficacy than plain gel.

Development of NLC- based Sunscreen Gel of Lutein and its in-vitro and ex-vivo Characterisation

Background: In humans, Carotenoids are important in scavenging singlet oxygen and peroxyl radicals. Lutein has been demonstrated in multiple studies to help protect the skin from photodamage, as well as provide a variety of other health advantages. In the recent decade, the topi-cal use of Lutein as a new ultraviolet (UV) protectant, anti-stress, and blue light filter capable of protecting skin from photodamage has piqued cosmetic and pharmacological attention. Because Lutein is insoluble, it was integrated into nanocarriers for topical administration. Objective: The objective of this study was to formulate an NLC-based sunscreen gel of Lutein. Method: Nanostructured lipid carriers (NLC) were prepared by melt emulsion ultrafiltration tech-nique and were evaluated for particle size, zeta potential, polydispersity index (PDI), drug loading (DL), encapsulation efficacy (EE), and in vitro drug release. The optimised formula was incorpo-rated into a gel base and an in-vitro sun protection factor (SPF) was determined. Ex- vivo permea-tion study was performed on rat skin using a Franz diffusion cell. Cocoa butter and rose oil were chosen as solid and liquid lipids for NLC formulation. Results: The particle size, PDI, zeta potential, entrapment efficiency, and in vitro drug release of optimised formulation (NLC5) were found to be 81.64 nm, 0.463, -14.1mV, 79.90 %, and 89.86% respectively. The SPF value of the Lutein-NLC-loaded gel was found to be 27.524. The drug flux Jss from NLC gel was measured in the range of 0.07955 g/cm2/h. Conclusion: The investigation suggested lipid nanoparticles as a suitable carrier for Lutein to be delivered as sunscreen gel.

Formulation and development of novel lipid-based combinatorial advanced nanoformulation for effective treatment of non-melanoma skin cancer

Non-melanoma skin cancer is one of the most common malignancies reported with high number of morbidities, demanding an advanced treatment option with superior chemotherapeutic effects. Due to high degree of drug resistance, conventional therapy fails to meet the desired therapeutic efficacy. To break the bottleneck, nanoparticles have been used as next generation vehicles that facilitate the efficient interaction with the cancer cells. Here, we developed combined therapy of 5-fluorouracil (5-FU) and cannabidiol (CBD)-loaded nanostructured lipid carrier gel (FU-CBD-NLCs gel). The NLCs were optimized using central composite design that showed an average particle size of 206 nm and a zeta potential of −34 mV. In addition, in vitro and ex vivo drug permeations studies demonstrated the effective delivery of both drugs in the skin layers via lipid structured nanocarriers. Also, the prepared FU-CBD-NLCs showed promising effect in-vitro cell studies including MTT assays, wound healing and cell cycle as compared to the conventional formulation. Moreover, dermatokinetic studies shows there was superior deposition of drugs at epidermal and the dermal layer when treated with FU-CBD-NLCs. In the end, overall study offered a novel combinatorial chemotherapy that could be an option for the treatment of non-melanoma skin cancer.

RETRACTED ARTICLE: Transdermal delivery of allopurinol-loaded nanostructured lipid carrier in the treatment of gout

BackgroundAllopurinol (ALP), a xanthine oxidase inhibitor, is a first line drug for the treatment of gout and hyperuricemia. Being the member of BCS class II drugs, ALP has solubility problem, which affects its bioavailability. Also, ALP has shorter half-life and showed GI related problems. In present study, ALP was encapsulated in nanostructured lipid carriers (NLCs) to ensure enhanced bioavailability, improved efficacy and safety in vivo.MethodologyALP-loaded NLCs were fabricated by micro-emulsion technique. The prepared NLCs were optimized via design expert in term of particle size, zeta potential and entrapment efficiency. FTIR, PXRD and TEM analysis were carried out to check chemical interaction, polymorphic form and surface morphology of the optimized formulation. ALP-loaded NLCs were then loaded into HPMC based poloxamer-407 gel and were characterized. In vitro and ex vivo analysis were carried out via dialysis membrane method and franz diffusion cell, respectively. Uric acid was used for induction of gout and the anti-gout activity of ALP-loaded NLCs gel was performed and compared with ALP suspension.ResultsThe optimized formulation had particles in nano-range (238.13 nm) with suitable zeta potential (-31.5 mV), poly-dispersity index (0.115) and entrapment of 87.24%. FTIR results confirmed absence of chemical interaction among formulation ingredients. XRD indicated amorphous nature of ALP-loaded NLCs, whereas TEM analysis confirmed spherical morphology of nanoparticles. The optimized formulation was successfully loaded in to gel and characterized accordingly. The in vitro release and drug release kinetics models showed sustained release of the drug from ALP-loaded NLCs gel. Furthermore, about 28 fold enhanced permeation was observed from ALP-loaded NLCs gel as compared to conventional gel. Skin irritation study disclosed safety of ALP-loaded NLCs gel for transdermal application. Furthermore, ALP-loaded NLCs gel showed significantly enhanced anti-gout activity in Sprague–Dawley rats after transdermal administration as compared to oral ALP suspension.ConclusionALP-loaded NLCs gel after transdermal administration sustained the drug release, avoid gastrointestinal side effects and enhance the anti-gout performance of ALP. It can be concluded, that NLCs have the potential to deliver drugs via transdermal route as indicated in case of allopurinol.

In Vitro and Ex Vivo Evaluation of Fluocinolone Acetonide-Acitretin-Coloaded Nanostructured Lipid Carriers for Topical Treatment of Psoriasis.

Psoriasis is chronic autoimmune disease that affects 2-5% of the global population. Fluocinolone acetonide (FLU) and acitretin (ACT) are widely used antipsoriatic drugs that belong to BCS classes II and IV, respectively. FLU exhibits side effects, such as skin irritation and a burning sensation. ACT also shows adverse effects, such as gingivitis, teratogenic effects and xerophthalmia. In the present study, topical nanostructured lipid carriers (NLCs) were fabricated to reduce the side effects and enhance the therapeutic efficacy. FLU-ACT-coloaded NLCs were prepared by the modified microemulsion method and optimized by the Box-Behnken model of Design Expert® version 12. The optimization was based on the particle size (PS), zeta potential (ZP) and percentage of encapsulation efficiency (%EE). The physicochemical analyses were performed by TEM, FTIR, XRD and DSC to assess the morphology, chemical interactions between excipients, crystallinity and thermal behavior of the optimized FLU-ACT-coloaded NLCs. The FLU-ACT-coloaded NLCs were successfully loaded into gel and characterized appropriately. The dialysis bag method and Franz diffusion cells were used for the in vitro release and ex vivo permeation studies, respectively. The optimized FLU-ACT-coloaded NLCs had the desired particle size of 288.2 ± 2.3 nm, ZP of -34.2 ± 1.0 mV and %EE values of 81.6 ± 1.1% for ACT and 75 ± 1.3% for FLU. The TEM results confirmed the spherical morphology, while the FTIR results showed the absence of chemical interactions of any type among the ingredients of the FLU-ACT-coloaded NLCs. The XRD and DSC analyses confirmed the amorphous nature and thermal behavior. The in vitro study showed the sustained release of the FLU and ACT from the optimized FLU-ACT-coloaded NLCs and FLU-ACT-coloaded NLC gel compared with the FLU-ACT suspension and conventional gel. The ex vivo study confirmed the minimal permeation of both drugs from the FLU-ACT-coloaded NLC gel.